ABSTRACT
Background: Adapted anti-SARS- CoV- 2 vaccination schedules have been recommended for patients with IMID due to a higher risk of reduced vaccine response. Nonetheless, there is little data on how different vaccine schedules influence immune responses and on the long-term persistence of vaccination responses in this subset. Purpose(s): The aim of this study is to assess the long-term course of humoral responses to SARS-CoV- 2 vaccines in a large prospective cohort of IMID patients and non-IMID controls with up to 10 months of follow-up following the first vaccine dose. Method(s): In February 2020, we started a prospective cohort of IMID patients and healthy controls (HC) to evaluate immune responses to SARS-CoV- 2 vaccines and infection (1). Individuals who provided data starting 4 weeks before their first vaccination and forward were included. Serum anti-SARS- CoV- 2 spike protein IgG were measured by ELISA (EUROIMMUN, Lubeck, Germany) in units of Optical density (OD) at 450 nm. An OD <1.1 was considered as poor response. We used time splines to fit linear mixed-effect models for log-transformed antibody levels and logistic mixed-effects models, adjusting for age and sex to estimate marginal mean antibody levels and adjusted risk of poor response with 95 percent confidence intervals. Antibody levels of twice-vaccinated patients were also compared to those who received 3 vaccinations. Result(s): Between December 2020 and December 2021, 3733 IMID patients and HC contributed 5564 samples, with a median (IQR) follow-up of 23.3 (13.9-0.9) weeks following first immunization (Table 1). By the date of their most recent sampling, 3280 (88%) participants had received two vaccines and 241 (6%) received three. Age and sex-adjusted estimated marginal mean IgG in IMID patients declined after week 10 and were significantly lower at all timepoints compared to controls (Figure 1A, Table 1). Adjusted risk of poor response at week 40 was 2.9% (1.4%-6.1%) in HC whereas 26.1% (15.8-40.0) in IMID (Figure 1B). After a median 20 (10-26). weeks from the second dose, 147 (6%) IMID patients had received a third dose. Adjusted mean antibody levels at 40 weeks in IMID patients who received three vaccine doses were higher than in HC who received two doses (Figure 1C). Conclusion(s): IMID patients had a weaker humoral response to SARS-CoV- 2 vaccination than controls at all time points following the first dose with a high risk of poor response at 40 weeks. Nonetheless, a third dose in IMID patients could provide higher antibody levels compared to unboosted healthy individuals.
ABSTRACT
Background: The frst vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated infammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identifed leading to specifc vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specifc recommendations are lacking. Objectives: To evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the frst vaccine dose. Methods: We have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their frst vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantifed with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We ftted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confdence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations. Results: Among 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the frst vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, fnally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B). Conclusion: Humoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the frst vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.
ABSTRACT
Background: Liquid biopsy technology has delivered promising results for therapy monitoring and disease relapse detection. The simplicity of the procedure makes it attractive for early cancer detection despite its clinical value in this setting being as yet unknown. The objective of the study is to evaluate the acceptance of this new screening technology by the general population. Methods: Participants in a digital health study originally selected randomly from the general population of the canton of Geneva (Switzerland) were invited to participate in a survey investigating (1) their motivation and (2) what factors might affect their decision regarding whether to proceed to a liquid biopsy test for cancer screening. Results: 2'898 participants responded to the survey (participation rate: 35%), 1'568 are > 50yo. Two thirds are female, 7.6% have a history of cancer, 80.8% have a family relative with a history of cancer. In the whole population: 97.7% are ready to use liquid biopsy as a cancer screening test. In the > 50yo, 97.3% of women and 98.5% of men would do the test. In the < 50yo, 97.2% of women and 98.6% of men would take it with X2 = 0.018 (p = 0.89) for independence with sex. Age category, education level, income band, professional status, self-rated health, tobacco status, chronic disease, personal or familial history of cancer and COVID pandemic have no statistical impact on the incentive to do a liquid biopsy test. In the whole population, 94.6% would take the test knowing that there is a risk of a false positive. The median accepted false positive percentage error rate is 10% with interquartile rate (IQR) Q1: 5% and Q3: 15%. Ninety-six percent of respondents would take the test knowing that there is a risk of a false negative, accepting a median false negative percentage error rate of 10% with IQR Q1: 5% and Q3 : 20%. Most respondents (97.6%) will do the test knowing that additional tests or procedures could be required in case of positivity and 58.8% would take it yearly, while 24.6% only every two years. Fifty-nine percent believe that taking the test could influence their lifestyle, regardless of the result. Conclusions: This study shows that the surveyed population is ready to engage with liquid biopsy as a cancer screening tool despite its limitations and drawbacks. Willingness to take the test might depend on sex only in the < 50yo population. Knowing the lack of demonstrated benefit, it is urgent to conduct trials assessing the clinical value, psychological impact and financial burden of liquid biopsy tests before incorporating this technology into cancer screening programs. Due to the very high level of interest demonstrated in our study, the possibility of direct-to-consumer availability should prompt health authorities and accreditation bodies to carefully weigh the impact of authorizing market access to liquid biopsy technologies for this purpose.
ABSTRACT
Background: SARS-CoV-2 vaccines have changed the course of the current global pandemic. Cancer patients were identified as highrisk of adverse infection outcomes. We have previously characterised the serological response to SARS-CoV-2 vaccines in 220 cancer patients treated at our institution. In addition these patients were given the possibility to report their symptoms (patient-reported outcomes, PROs) weekly using a digital platform (ePROs). We sought to determine if, in cancer patients, the prospectively recorded post-vaccination ePROs could predict the serological response to SARS-CoV-2 vaccines. Methods: We used a pre-existing digital platform that allows monitoring of PROs using weekly questionnaires sent to patients and available on their desktop computers, tablets or smartphones. Serial serologies were performed at 28, 50 and 115 days after vaccination. Results: We observed that at day 50 after the first vaccination dose, coinciding with three weeks after the second dose, patients could be divided into two groups according to their serological response (low - below 1500 U/ml and high - above or equal 1500 U/ml). A peak in symptom burden could be observed after the second dose, as previously described. Omitting ePRO features decreased prediction performance of all models, whereas omitting baseline symptom scores had inconsistent effects. Among all models and feature constructions, the top performance metrics were given by the nearest centroid model7 with baseline symptoms omitted and 20 features chosen with the aforementioned procedure. The model achieved an accuracy of 0.704, an F1-score of 0.759 and an MCC of 0.398. Conclusions: we were able to identify the patients who achieved higher antibody levels against SARS-COV-2 based on the symptom burden reported through ePROs. This represents the first model showing that symptoms, assessed through ePRO can be predictive of response to vaccines. Our results could also be useful information for patients, as they could assuage their fears about adverse -effects, through the knowledge that toxicity could predict better protection against SARS-COV-2. The same toxicity-based prediction of efficacy has been identified with immunotherapy in cancer and is now a routine part of clinical discussions with patients.
ABSTRACT
Medical oncologists are steering a difficult course during the COVID-19 pandemic between three opposing forces: revisiting optimal standards of cancer care, facing constantly evolving shortages as some resources are being redirected, and acknowledging the paradoxical need to keep patients away from the health care facility. This article compiles recommendations from cancer societies and expert opinions to provide guidance and practical solutions for the oncology clinic. We propose that optimal standards of care be upheld, and short-term safety concerns due to exposure to SARS-CoV-2 be weighed against a long-term compromise in cancer prognosis when deciding on adjustments in cancer care. Proper mitigation strategies in the clinic and use of less resource-heavy but equivalent treatment alternatives often allow optimal cancer care. The magnitude of benefit of cancer treatments needs to be systematically considered.